The main purpose of this project is to evaluate, in a double blind, randomized, placebo controlled clinical trial, the chemopreventive efficacy and safety of a very promising food supplement - Polyphenon E (decaffeinated green tea polyphenol mixture), in smokers with bronchial intraepithelial neoplasia (IEN). 2,574 former heavy smokers (> 30 pack-years) > 45 years of age without evidence of overt lung cancer will be recruited over a 42 months period by an experienced clinical trial team with a track record of completing several consecutive NCI-sponsored chemoprevention trials on schedule. A unique sputum induction method combining high frequency chest wall oscillation and hypertonic saline nebulization will be used to reduce unsatisfactory sputum samples rate to <3%. Image analysis of sputum will be used to identify individuals harboring IEN lesions and to reduce the number of unproductive bronchoscopies by over 50%. A newly developed quantitative autofluorescence bronchoscopy method will be used to localize IEN lesions > 1.2 mm (bigger than the size of a bronchial biopsy). One-hundred and ten subjects with one or more IEN lesions >1.2 mm will receive Polyphenon E 1.6 g daily/Placebo for 6 months. The primary endpoint of the study will be combined nuclear morphometry and histopathology on bronchial biopsies before and 6 months after treatment. This surrogate endpoint biomarker (SEB) was developed and refined through several previous NCI sponsored trials. An innovative optical imaging technology - confocal microendoscopy, will be developed as a non-biopsy method to assess the effect of chemopreventive agents. Methylation of several biomarkers in sputa, bronchial brushes as well as BAL cells will be tested as SEB in central and peripheral airways and in surrogate organs using quantitative real time PCR. The extent to which clinical-pathological response, modulation of cell cycle, cellular proliferation, and apoptosis in human can be correlated with those in animal tumor models will be determined by measuring the same biomarkers in the A/J mouse and hamster lung tumor models before and after treatment with Polyphenon E. The results will provide new information on the efficacy and safety of Polyphenon E for the chemoprevention of lung cancer. It will also provide new information on the use of SEBs for assessing the effect of chemoprevention.